What makes a cell pluripotent?

Pluripotent stem cells (PSC) can generate any cell type in the organism. Therefore, PSCs could potentially form the basis of therapies that replace damaged or missing cells -- for example in neurodegenerative disorders. Most organisms that are used in research do not have pluripotent stem cells in the adult making it challenging to study how pluripotency persists in normal, physiological, conditions. We use planarians, freshwater flatworms, animals that have an abundant population of PSCs. Planarians use PSCs for tissue maintenance and for regeneration. We are particularly interested in the regulation of differentiation vs. proliferation of planarian stem cells, and how the balance of these processes allow the animals to regenerate.

Shown is a planrian labeled in magenta for an abudnant neoblast marker (smedwi-1). Neoblasts are found through the animal except for the pharynx and the head tip.

Conserved stem cell functions

We are interested in the evolution of stem cells, their developmental potential, and their functions across the animal kingdom. We use various techniques, including single-cell RNA sequencing (SCS) to computationally determine cellular identities and lineage potential, and most importantly, their functions.

Major cell types
Major cell types

Single-cell RNA sequencing of planarian cells reveals the ajor planarian cell types. Gene expression is represented using a tSNE plot, where each dot represents the gene expression of a single cell. Density-based clustering was used to assign cells to clusters, and the identity of each cluster was determined using published and novel gene expression markers.

Epidermal differentiation
Epidermal differentiation

Differentiation of the planarian epidermis from neoblasts to fully mature cells revealed by single cell RNA sequencing. Each dot represents the gene expression of a single cell colored based on the stage of maturation.

kal1 expression by ISH
kal1 expression by ISH

A lateral view of a planarian showing the expression of the ventral specific marker, kal1. The arrow indicates the ventral side of the animal.

Major cell types
Major cell types

Single-cell RNA sequencing of planarian cells reveals the ajor planarian cell types. Gene expression is represented using a tSNE plot, where each dot represents the gene expression of a single cell. Density-based clustering was used to assign cells to clusters, and the identity of each cluster was determined using published and novel gene expression markers.

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Wound response across the animal kingdom

All animals developed mechanisms to survive injuries, including transcriptional programs that are activated in response to wounding. Despite the critical contribution of these transcriptional responses to recovery and healing, it is unknown whether they are conserved across the phylogeny, and how they evolved in organisms with different survival and regenerative capacities. Finding the conserved components of the injury response is essential for understanding the differences in survival and regenerative capacities of different organisms. We use comparative genomics for unraveling the conserved regulatory circuitry of injury-response and harness the planarian system to study its conserved functions.